ID SULF1_RAT Reviewed; 870 AA.
AC Q8VI60;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 24-JAN-2024, entry version 115.
DE RecName: Full=Extracellular sulfatase Sulf-1;
DE AltName: Full=Arylsulfatase;
DE EC=3.1.6.1 {ECO:0000250|UniProtKB:Q8IWU6};
DE AltName: Full=N-acetylglucosamine-6-sulfatase;
DE EC=3.1.6.14 {ECO:0000250|UniProtKB:Q8IWU6};
DE AltName: Full=RSulfFP1;
DE AltName: Full=Sulfatase FP;
DE Contains:
DE RecName: Full=Extracellular sulfatase Sulf-2 secreted form {ECO:0000250|UniProtKB:Q8IWU6};
DE Flags: Precursor;
GN Name=Sulf1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=11895481; DOI=10.1046/j.1356-9597.2001.00502.x;
RA Ohto T., Uchida H., Yamazaki H., Keino-Masu K., Matsui A., Masu M.;
RT "Identification of a novel nonlysosomal sulphatase expressed in the floor
RT plate, choroid plexus and cartilage.";
RL Genes Cells 7:173-185(2002).
RN [2]
RP ERRATUM OF PUBMED:11895481.
RA Ohto T., Uchida H., Yamazaki H., Keino-Masu K., Matsui A., Masu M.;
RL Genes Cells 7:521-522(2002).
CC -!- FUNCTION: Exhibits arylsulfatase activity and highly specific
CC endoglucosamine-6-sulfatase activity (By similarity). It can remove
CC sulfate from the C-6 position of glucosamine within specific subregions
CC of intact heparin (By similarity). Diminishes HSPG (heparan sulfate
CC proteoglycans) sulfation, inhibits signaling by heparin-dependent
CC growth factors, diminishes proliferation, and facilitates apoptosis in
CC response to exogenous stimulation (By similarity).
CC {ECO:0000250|UniProtKB:Q8IWU6}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aryl sulfate + H2O = a phenol + H(+) + sulfate;
CC Xref=Rhea:RHEA:17261, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16189, ChEBI:CHEBI:33853, ChEBI:CHEBI:140317; EC=3.1.6.1;
CC Evidence={ECO:0000250|UniProtKB:Q8IWU6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of the 6-sulfate groups of the N-acetyl-D-
CC glucosamine 6-sulfate units of heparan sulfate and keratan sulfate.;
CC EC=3.1.6.14; Evidence={ECO:0000250|UniProtKB:Q8IWU6};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P15289};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250|UniProtKB:P15289};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:11895481}. Golgi apparatus, Golgi stack
CC {ECO:0000269|PubMed:11895481}. Cell surface
CC {ECO:0000269|PubMed:11895481}.
CC -!- SUBCELLULAR LOCATION: [Extracellular sulfatase Sulf-2 secreted form]:
CC Secreted {ECO:0000250|UniProtKB:Q8IWU6}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in the floor plate, choroid
CC plexus and cartilage. Weaker expression seen in the eye, lung brain,
CC spinal cord, urinary bladder, testis, ovary and uterus.
CC {ECO:0000269|PubMed:11895481}.
CC -!- DEVELOPMENTAL STAGE: Abundantly and specifically expressed in the floor
CC plate region of the spinal cord at embryonic day 13 (13 dpc) and 15 dpc
CC and at lower levels at postnatal day 1 (P1). A high level expression
CC was also observed in the ventral hindbrain and midbrain. No expression
CC was seen in the notochord at these stages. Prominent expression in the
CC nervous system was also seen in the choroid plexus. At 13 dpc,
CC expression was also seen in the dorsomedial forebrain and roof of the
CC hind brain. Robust and specific expression was detected in the choroid
CC plexus epithelium of the lateral, 3rd and 4th ventricles at 15 dpc and
CC P1 and persisted into adulthood. In the CNS, expression was detected in
CC thalamic and hypothalamic regions at 13 dpc, 15 dpc and P1. In embryos,
CC it was highly expressed in the limb buds, face region, large blood
CC vessels, olfactory pits and pleural epithelium. In particular,
CC expression was robust and specific in bone-forming regions of the face
CC and in the mesenchymal cells surrounding the developing cartilages of
CC the extremities. {ECO:0000269|PubMed:11895481}.
CC -!- PTM: Processing by furin produces a secreted form.
CC {ECO:0000250|UniProtKB:Q8IWU6}.
CC -!- PTM: The conversion to 3-oxoalanine (also known as C-formylglycine,
CC FGly), of a serine or cysteine residue in prokaryotes and of a cysteine
CC residue in eukaryotes, is critical for catalytic activity.
CC {ECO:0000250|UniProtKB:P15289}.
CC -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
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DR EMBL; AF230072; AAL71906.1; -; mRNA.
DR RefSeq; NP_599205.1; NM_134378.2.
DR AlphaFoldDB; Q8VI60; -.
DR SMR; Q8VI60; -.
DR STRING; 10116.ENSRNOP00000064072; -.
DR GlyCosmos; Q8VI60; 10 sites, No reported glycans.
DR GlyGen; Q8VI60; 10 sites.
DR PhosphoSitePlus; Q8VI60; -.
DR PaxDb; 10116-ENSRNOP00000012611; -.
DR Ensembl; ENSRNOT00055029624; ENSRNOP00055023787; ENSRNOG00055017510.
DR Ensembl; ENSRNOT00060003072; ENSRNOP00060002058; ENSRNOG00060001963.
DR Ensembl; ENSRNOT00065017652; ENSRNOP00065013551; ENSRNOG00065010873.
DR GeneID; 171396; -.
DR KEGG; rno:171396; -.
DR UCSC; RGD:708554; rat.
DR AGR; RGD:708554; -.
DR CTD; 23213; -.
DR RGD; 708554; Sulf1.
DR eggNOG; KOG3731; Eukaryota.
DR InParanoid; Q8VI60; -.
DR OrthoDB; 1365192at2759; -.
DR PhylomeDB; Q8VI60; -.
DR PRO; PR:Q8VI60; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005795; C:Golgi stack; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0004065; F:arylsulfatase activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005539; F:glycosaminoglycan binding; IBA:GO_Central.
DR GO; GO:0008449; F:N-acetylglucosamine-6-sulfatase activity; ISS:UniProtKB.
DR GO; GO:0060348; P:bone development; ISS:UniProtKB.
DR GO; GO:0001502; P:cartilage condensation; ISS:UniProtKB.
DR GO; GO:0051216; P:cartilage development; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0002063; P:chondrocyte development; ISS:UniProtKB.
DR GO; GO:0048706; P:embryonic skeletal system development; ISS:UniProtKB.
DR GO; GO:0014846; P:esophagus smooth muscle contraction; ISS:UniProtKB.
DR GO; GO:0035860; P:glial cell-derived neurotrophic factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032836; P:glomerular basement membrane development; ISO:RGD.
DR GO; GO:0003094; P:glomerular filtration; ISO:RGD.
DR GO; GO:0030201; P:heparan sulfate proteoglycan metabolic process; ISS:UniProtKB.
DR GO; GO:0060384; P:innervation; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0036022; P:limb joint morphogenesis; ISS:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060686; P:negative regulation of prostatic bud formation; ISS:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:RGD.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
DR CDD; cd16147; G6S; 1.
DR Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR014615; Extracellular_sulfatase.
DR InterPro; IPR024609; Extracellular_sulfatase_C.
DR InterPro; IPR024607; Sulfatase_CS.
DR InterPro; IPR000917; Sulfatase_N.
DR PANTHER; PTHR43108:SF1; EXTRACELLULAR SULFATASE SULF-1; 1.
DR PANTHER; PTHR43108; N-ACETYLGLUCOSAMINE-6-SULFATASE FAMILY MEMBER; 1.
DR Pfam; PF12548; DUF3740; 2.
DR Pfam; PF00884; Sulfatase; 1.
DR PIRSF; PIRSF036665; Sulf1; 1.
DR SUPFAM; SSF53649; Alkaline phosphatase-like; 2.
DR PROSITE; PS00523; SULFATASE_1; 1.
PE 2: Evidence at transcript level;
KW Calcium; Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Hydrolase;
KW Metal-binding; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..870
FT /note="Extracellular sulfatase Sulf-1"
FT /id="PRO_0000033436"
FT CHAIN 545..870
FT /note="Extracellular sulfatase Sulf-2 secreted form"
FT /evidence="ECO:0000250|UniProtKB:Q8IWU5"
FT /id="PRO_0000457758"
FT REGION 1..414
FT /note="Catalytic domain; necessary for arylsulfatase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q8IWU5"
FT REGION 415..733
FT /note="Hydrophilic domain; necessary for endoglucosamine-6-
FT sulfatase activity"
FT /evidence="ECO:0000250|UniProtKB:Q8IWU5"
FT REGION 506..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 847..870
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 506..527
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 87
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 51
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 52
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 87
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /note="via 3-oxoalanine"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 316
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 317
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT SITE 544..545
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000250|UniProtKB:Q8IWU5"
FT MOD_RES 87
FT /note="3-oxoalanine (Cys)"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 622
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 772
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 782
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 870 AA; 100860 MW; 037813868C08967F CRC64;
MKNSCWALLL AVLGAELLGG FCSTMRSQRF RGRVQQERKN IRPNIILVLT DDQDVELGSL
QVMNKTRKIM EHGGATFTNA FVTTPMCCPS RSSMLTGKYV HNHNVYTNNE NCSSPSWQAL
HEPRTFAVYL NNTGYRTAFF GKYLNEYNGS YIPPGWREWL GLIKNSRFYN YTVCRNGIKE
KHGFDYAKDY FTDLITNESI NYFKMSKRMY PHRPVMMVIS HAAPHGPEDS APQFSKLYPN
ASQHITPSYN YAPNMDKHWI MQYTGPMLPI HMEFTNVLQR KRLQTLMSVD DSVERLYNML
VETGELGNTY IIYTADHGYH IGQFGLVKGK SMPYDFDIRV PFFIRGPSIE PGSIVPQIVL
NIDLAPTILD IAGLDTPSDV DGKSVLKLLD LEKPGNRFRT NKKAKIWRDT FLVERGKFLR
KKEESSKNIQ QSNHLPKYER VKELCQQARY QTACEQPGQN WQCIEDTSGK LRIHKCKGPS
DLLTVRQNAR NLYSRGLQDK DKECHCRESG YRPSRSQRKK ERQFLRNQGT PKYKPRFVHT
RQTRSLSVEF EGEIYDINLE EEELQVLPPR SVAKRHDEGH QGFGGHQAAA GDFRNEMLAD
SNSAVGLPTT VRVTHKCFIL PNDTIHCERE LYQSARAWKD HKAYIDKEIE VLQDKIKNLR
EVRGHLKKRK PEECSCGKQS YYNKEKGVKR QEKLKSHLHP FKEAAAQEVD SKLQLFKEHR
RRKKERKEKK RQRKGEECSL PGLTCFTHDN NHWQTAPFWN LGSFCACTSS NNNTYWCLRT
VNETHNFLFC EFATGFLEYF DMNTDPYQLT NTVHTVERGI LNQLHIQLME LRSCQGYKQC
NPRPKSLDVG TKEGGNYDPH RGQLWDGWEG
//
